Smoking Causes Cancer, Now We Know Exactly How

That cigarette smoke — a deadly cocktail of over 70 known carcinogens — can have a deleterious effect on human health is nothing to write home about. However, the exact mechanism through which smoking damages the genome and ultimately increases the risk of at least 17 classes of cancer is something that is still not fully understood.

A new computational study that studied the “archaeological record” of mutations associated with cancer in over 5,200 genomes has now revealed that smoking tobacco increases cancer risk by not only damaging DNA in organs directly exposed, but also by disrupting cell function in organs that are indirectly exposed to the smoke.

“Our research indicates that the way tobacco smoking causes cancer is more complex than we thought,” the study’s joint lead author Mike Stratton from the Wellcome Trust Sanger Institute in Cambridge, U.K., said in a statement released Thursday. “Indeed, we do not fully understand the underlying causes of many types of cancer and there are other known causes, such as obesity, about which we understand little of the underlying mechanism. This study of smoking tells us that looking in the DNA of cancers can provide provocative new clues to how cancers develop and thus, potentially, how they can be prevented.”

As part of the study, the researchers used a pattern-recognition software to analyze mutational “signatures” in genome sequences of smoking-related cancers and compared them to cancer cells of nonsmokers. They discovered over 20 mutational signatures across the 17 cancer types associated with tobacco smoking, and, of these, five were elevated in cancer cells extracted from smokers. Some cancer types had only a single mutational signature elevated in smokers, while others had multiple.

One of these signatures, called signature 4, was traced to DNA being damaged by direct exposure to tobacco smoke. Another one, signature 5, was found in all cells and was correlated with increased mutation rates in smokers than in nonsmokers.

“Our analysis demonstrates that tobacco smoking causes mutations that lead to cancer by multiple distinct mechanisms,” co-lead author Ludmil Alexandrov from the Los Alamos National Laboratory, New Mexico, said in the statement. “Tobacco smoking damages DNA in organs directly exposed to smoke as well as speeds up a mutational cellular clock in organs that are both directly and indirectly exposed to smoke.”

The researchers also quantified the impact of cigarette smoke on the human body. They estimated that, on average, smoking a pack of cigarettes (20 cigarettes) a day led to 150 mutations in each lung cell every year, drastically increasing the likelihood that the cell could become cancerous. In addition, cells in larynx — the voice box — the mouth, and the pharynx — part of the oral cavity behind the nose and the mouth — were also significantly affected.

“There is a message here for people who are occasional or social smokers who think it doesn’t do anything,” Alexandrov told the Guardian. “If you smoke four to five packs of cigarettes in your lifetime it doesn’t sound that much, but you still get several mutations in every cell in your lungs and these are permanent, they do not go away. … If you stop smoking, they’ll still be there.”